Epzicom

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Epzicom falls into category C. In animal studies, pregnant animals were given this medication and had some babies born with problems. No well-controlled studies have been done in humans. Therefore, this medication may be used if the potential benefits to the mother outweigh the potential risks to the unborn child.

If you take Epzicom while you are pregnant, talk to your healthcare provider about how you can take part in the Pregnancy Registry for Epzicom. The purpose of the pregnancy registry is to collect information about the health of you and your baby.

Tell your doctor if you are breastfeeding or plan to breastfeed. The Centers for Disease Control and Prevention recommend that HIV-1-infected mothers not breastfeed their infants to avoid risk of HIV-1 transmission. Both medicines in Epzicom may be excreted in human breast milk. Because of both the potential for HIV-1 transmission and the potential for serious adverse reactions in nursing infants, your doctor advise you not to breastfeed while taking Epzicom.

WARNING: RISK OF HYPERSENSITIVITY REACTIONS, LACTIC ACIDOSIS AND SEVERE HEPATOMEGALY, AND EXACERBATIONS OF HEPATITIS

Hypersensitivity Reactions: Serious and sometimes fatal hypersensitivity reactions have been associated with abacavir sulfate, a component of this medication (Epzicom ).

Hypersensitivity Reactions: Serious and sometimes fatal hypersensitivity reactions have been associated with abacavir sulfate. Hypersensitivity to abacavir is a multi-organ clinical syndrome usually characterized by a sign or symptom in 2 or more of the following groups: 

• Discontinue this medication as soon as a hypersensitivity reaction is suspected.

Patients who carry the HLA-B*5701 allele are at high risk for experiencing a hypersensitivity reaction to abacavir. Prior to initiating therapy with abacavir, screening for the HLA-B*5701 allele is recommended; this approach has been found to decrease the risk of hypersensitivity reaction. Screening is also recommended prior to reinitiation of abacavir in patients of unknown HLA-B*5701 status who have previously tolerated abacavir. HLA-B*5701-negative patients may develop a suspected hypersensitivity reaction to abacavir; however, this occurs significantly less frequently than in HLA-B*5701-positive patients.

Regardless of HLA-B*5701 status, permanently discontinue this medication if hypersensitivity cannot be ruled out, even when other diagnoses are possible.

Following a hypersensitivity reaction to abacavir, NEVER restart this medication or any other abacavir-containing product because more severe symptoms can occur within hours and may include life-threatening hypotension and death.

Reintroduction of this medication or any other abacavir-containing product, even in patients who have no identified history or unrecognized symptoms of hypersensitivity to abacavir therapy, can result in serious or fatal hypersensitivity reactions. Such reactions can occur within hours.

Lactic Acidosis and Severe Hepatomegaly: Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination, including abacavir, lamivudine, and other antiretrovirals

Exacerbations of Hepatitis B: Severe acute exacerbations of hepatitis B have been reported in patients who are co-infected with hepatitis B virus (HBV) and human immunodeficiency virus (HIV-1) and have discontinued lamivudine, which is one component of this medication. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue this medication and are co-infected with HIV-1 and HBV. If appropriate, initiation of anti-hepatitis B therapy may be warranted.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Abdominal or stomach pain
• cough
• diarrhea
• fever
• headache
• nausea
• numbness or tingling of the face, feet, or hands
• pain in the joints
• pain in the muscles
• skin rash
• sore throat
• swelling of the feet or lower legs
• unusual feeling of discomfort or illness
• unusual tiredness or weakness
• vomiting

• Blistering, peeling, or loosening of the skin
• bloating
• burning, numbness, tingling, or painful sensations
• chest pain
• chills
• constipation
• convulsions
• dark urine
• decreased appetite
• diarrhea
• difficulty with swallowing
• dizziness
• fast heartbeat
• fast, shallow breathing
• feeling of fullness
• general feeling of discomfort
• hives or welts, itching
• indigestion
• light-colored stools
• loss of appetite
• loss of bladder control
• muscle cramping
• muscle spasm or jerking of all extremities
• pains in the stomach, side, or abdomen, possibly radiating to the back
• pale skin
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• red, irritated eyes
• redness of the skin
• red skin lesions, often with a purple center
• sleepiness
• sores, ulcers, or white spots on the lips or in the mouth
• sudden loss of consciousness
• swollen, painful, or tender lymph glands in the neck, armpit, or groin
• tightness in the chest
• troubled breathing with exertion
• unsteadiness or awkwardness
• unusual bleeding or bruising
• upper right abdominal or stomach pain
• weakness in the arms, hands, legs, or feet
• yellow eyes and skin

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Abnormal dreams
• burning feeling in the chest or stomach
• fear or nervousness
• feeling of constant movement of self or surroundings
• lightheadedness
• sensation of spinning
• severe and throbbing headache
• stomach upset
• tenderness in the stomach area
• trouble sleeping

• Abnormal breathing sounds
• blurred vision
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• dry mouth
• flushed, dry skin
• fruit-like breath odor
• gaining weight around your neck, upper back, breast, face, or waist
• hair loss
• increased hunger
• increased thirst
• increased urination
• muscle weakness
• sweating
• swelling or inflammation of the mouth
• thinning of the hair
• unexplained weight loss

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• This medicine comes with an extra patient fact sheet called a Medication Guide. Read it with care. Read it again each time Epzicom is refilled. If you have any questions about this medicine, please talk with the doctor, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take Epzicom or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to Epzicom (abacavir and lamivudine). This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

Pregnancy

Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to Epzicom during pregnancy. Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263.

Risk Summary

Available data from the APR show no difference in the overall risk of birth defects for abacavir or lamivudine compared with the background rate for birth defects of 2.7% in the Metropolitan Atlanta Congenital Defects Program (MACDP) reference population [see Data]. The APR uses the MACDP as the U.S. reference population for birth defects in the general population. The MACDP evaluates women and infants from a limited geographic area and does not include outcomes for births that occurred at less than 20 weeks gestation. The rate of miscarriage is not reported in the APR. The estimated background rate of miscarriage in clinically recognized pregnancies in the U.S. general population is 15% to 20%. The background risk for major birth defects and miscarriage for the indicated population is unknown.

In animal reproduction studies, oral administration of abacavir to pregnant rats during organogenesis resulted in fetal malformations and other embryonic and fetal toxicities at exposures 35 times the human exposure (AUC) at the recommended clinical daily dose. However, no adverse developmental effects were observed following oral administration of abacavir to pregnant rabbits during organogenesis, at exposures approximately 9 times the human exposure (AUC) at the recommended clinical dose. Oral administration of lamivudine to pregnant rabbits during organogenesis resulted in embryolethality at systemic exposure (AUC) similar to the recommended clinical dose; however, no adverse development effects were observed with oral administration of lamivudine to pregnant rats during organogenesis at plasma concentrations (Cmax) 35 times the recommended clinical dose [see Data].

Data

Human Data: Abacavir: Based on prospective reports to the APR of over 2,000 exposures to abacavir during pregnancy resulting in live births (including over 1,000 exposed in the first trimester), there was no difference between the overall risk of birth defects for abacavir compared with the background birth defect rate of 2.7% in the U.S. reference population of the MACDP. The prevalence of defects in live births was 2.9% (95% CI: 2.0% to 4.1%) following first trimester exposure to abacavir-containing regimens and 2.7% (95% CI: 1.9% to 3.7%) following second/third trimester exposure to abacavir-containing regimens.

Abacavir has been shown to cross the placenta and concentrations in neonatal plasma at birth were essentially equal to those in maternal plasma at delivery [see Clinical Pharmacology (12.3)].

Lamivudine: Based on prospective reports to the APR of over 11,000 exposures to lamivudine during pregnancy resulting in live births (including over 4,500 exposed in the first trimester), there was no difference between the overall risk of birth defects for lamivudine compared with the background birth defect rate of 2.7% in the U.S. reference population of the MACDP. The prevalence of birth defects in live births was 3.1% (95% CI: 2.6% to 3.6%) following first trimester exposure to lamivudine-containing regimens and 2.8% (95% CI: 2.5%, 3.3%) following second/third trimester exposure to lamivudine-containing regimens.

Lamivudine pharmacokinetics were studied in pregnant women during 2 clinical trials conducted in South Africa. The trials assessed pharmacokinetics in 16 women at 36 weeks gestation using 150 mg lamivudine twice daily with zidovudine, 10 women at 38 weeks gestation using 150 mg lamivudine twice daily with zidovudine, and 10 women at 38 weeks gestation using lamivudine 300 mg twice daily without other antiretrovirals. These trials were not designed or powered to provide efficacy information. Lamivudine concentrations were generally similar in maternal, neonatal, and umbilical cord serum samples. In a subset of subjects, amniotic fluid specimens were collected following natural rupture of membranes and confirmed that lamivudine crosses the placenta in humans. Based on limited data at delivery, median (range) amniotic fluid concentrations of lamivudine were 3.9 (1.2 to 12.8)-fold greater compared with paired maternal serum concentration (n = 8).

Animal Data: Abacavir: Abacavir was administered orally to pregnant rats (at 100, 300, and 1,000 mg per kg per day) and rabbits (at 125, 350, or 700 mg per kg per day) during organogenesis (on gestation Days 6 through 17 and 6 through 20, respectively). Fetal malformations (increased incidences of fetal anasarca and skeletal malformations) or developmental toxicity (decreased fetal body weight and crown‑rump length) were observed in rats at doses up to 1,000 mg per kg per day, resulting in exposures approximately 35 times the human exposure (AUC) at the recommended daily dose. No developmental effects were observed in rats at 100 mg per kg per day, resulting in exposures (AUC) 3.5 times the human exposure at the recommended daily dose. In a fertility and early embryo-fetal development study conducted in rats (at 60, 160, or 500 mg per kg per day), embryonic and fetal toxicities (increased resorptions, decreased fetal body weights) or toxicities to the offspring (increased incidence of stillbirth and lower body weights) occurred at doses up to 500 mg per kg per day. No developmental effects were observed in rats at 60 mg per kg per day, resulting in exposures (AUC) approximately 4 times the human exposure at the recommended daily dose. Studies in pregnant rats showed that abacavir is transferred to the fetus through the placenta. In pregnant rabbits, no developmental toxicities and no increases in fetal malformations occurred at up to the highest dose evaluated, resulting in exposures (AUC) approximately 9 times the human exposure at the recommended dose.

Lamivudine: Lamivudine was administered orally to pregnant rats (at 90, 600, and 4,000 mg per kg per day) and rabbits (at 90, 300 and 1,000 mg per kg per day and at 15, 40, and 90 mg per kg per day) during organogenesis (on gestation Days 7 through 16 [rat] and 8 through 20 [rabbit]). No evidence of fetal malformations due to lamivudine was observed in rats and rabbits at doses producing plasma concentrations (Cmax) approximately 35 times higher than human exposure at the recommended daily dose. Evidence of early embryolethality was seen in the rabbit at systemic exposures (AUC) similar to those observed in humans, but there was no indication of this effect in the rat at plasma concentrations (Cmax) 35 times higher than human exposure at the recommended daily dose. Studies in pregnant rats showed that lamivudine is transferred to the fetus through the placenta. In the pre-and postnatal development study in rats, lamivudine was administered orally at doses of 180, 900, and 4,000 mg per kg per day from gestation Day 6 through postnatal Day 20). In the study, development of the offspring, including fertility and reproductive performance, were not affected by the maternal administration of lamivudine.

Lactation

Risk Summary

The Centers for Disease Control and Prevention recommend that HIV‑1‑infected mothers in the United States not breastfeed their infants to avoid risking postnatal transmission of HIV‑1 infection. Abacavir and lamivudine are present in human milk. There is no information on the effects of abacavir and lamivudine on the breastfed infant or the effects of the drug on milk production. Because of the potential for (1) HIV‑1 transmission (in HIV-negative infants), (2) developing viral resistance (in HIV-positive infants), and (3) serious adverse reactions in a breastfed infant, instruct mothers not to breastfeed if they are receiving Epzicom.

Pediatric Use

The dosing recommendations in this population are based on the safety and efficacy established in a controlled trial conducted using either the combination of EPIVIR and ZIAGEN or Epzicom [see Dosage and Administration (2.3), Adverse Reactions (6.2), Clinical Studies (14.2)].

In pediatric patients weighing less than 25 kg, use of abacavir and lamivudine as single products is recommended to achieve appropriate dosing.

Geriatric Use

Clinical trials of abacavir and lamivudine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. In general, caution should be exercised in the administration of Epzicom in elderly patients reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy [see Dosage and Administration (2.4), Use in Specific Populations (8.6, 8.7)].

Patients with Impaired Renal Function

Epzicom is not recommended for patients with creatinine clearance less than 50 mL per min because Epzicom is a fixed-dose combination and the dosage of the individual components cannot be adjusted. If a dose reduction of lamivudine, a component of Epzicom, is required for patients with creatinine clearance less than 50 mL per min, then the individual components should be used [see Clinical Pharmacology (12.3)].

Patients with Impaired Hepatic Function

Epzicom is a fixed-dose combination and the dosage of the individual components cannot be adjusted. If a dose reduction of abacavir, a component of Epzicom, is required for patients with mild hepatic impairment (Child-Pugh Class A), then the individual components should be used [see Clinical Pharmacology (12.3)].

The safety, efficacy, and pharmacokinetic properties of abacavir have not been established in patients with moderate (Child-Pugh Class B) or severe (Child-Pugh Class C) hepatic impairment; therefore, Epzicom is contraindicated in these patients [see Contraindications (4)].

Epzicom contains a combination of abacavir and lamivudine. Abacavir and lamivudine are both antiviral medicines that prevent human immunodeficiency virus (HIV) from multiplying in your body.

Epzicom is used to treat HIV, which can cause the acquired immunodeficiency syndrome (AIDS).

Epzicom is not a cure for HIV or AIDS.

You should not use Epzicom if you are allergic to abacavir or lamivudine, or:

• if you have liver disease;

• if you have ever tested positive for a gene variation called HLA-B*5701; or

• if you have ever had an allergic reaction to any medicine that contains abacavir or lamivudine (Combivir, Epivir, Triumeq, Trizivir, Ziagen).

Once you have had an allergic reaction to abacavir, you must never use it again.

Some people taking lamivudine develop a serious condition called lactic acidosis. This may be more likely in women, in people who are overweight or have liver disease, and in people who have taken HIV/AIDS medication for a long time. Talk with your doctor about your risk.

To make sure Epzicom is safe for you, tell your doctor if you have:

• hepatitis C (especially if you are treated with interferon and/or ribavirin);

• a history of hepatitis or other liver problems (especially hepatitis B);

• kidney disease;

• heart disease or high blood pressure;

• a risk factor for heart disease (such as smoking, diabetes, high cholesterol); or

• if you drink alcohol daily.

You may need a blood test before you start taking Epzicom for the first time, or if you are restarting the medicine after stopping for reasons not related to an allergic reaction.

It is not known whether Epzicom will harm an unborn baby. HIV can be passed to your baby if you are not properly treated during pregnancy. Tell your doctor if you are pregnant or plan to become pregnant during treatment. Take all of your HIV medicines as directed to control your infection.

If you are pregnant, your name may be listed on a pregnancy registry. This is to track the outcome of the pregnancy and to evaluate any effects of Epzicom on the baby.

Women with HIV or AIDS should not breast-feed a baby. Even if your baby is born without HIV, the virus may be passed to the baby in your breast milk.

Epzicom should not be given to a child who weighs less than 55 pounds.

Usual Adult Dose of Epzicom for HIV Infection:

1 tablet orally once a day

Use: In combination with other antiretroviral agents, for the treatment of HIV-1 infection

Usual Adult Dose of Epzicom for Nonoccupational Exposure:

US CDC recommendations: 1 tablet orally once a day
Duration of therapy: 28 days

Comments:
-Recommended as part of alternative regimens (NNRTI-based, protease inhibitor-based, or triple NRTI) for nonoccupational postexposure prophylaxis of HIV infection
-Prophylaxis should be started as soon as possible, within 72 hours of exposure.
-Current guidelines should be consulted for additional information.

Usual Adult Dose of Epzicom for Occupational Exposure:

US Public Health Service working group recommendations: 1 tablet orally once a day
Duration of therapy: 28 days, if tolerated

Comments:
-Only with expert consultation, as part of an alternative regimen for use as HIV postexposure prophylaxis
-Prophylaxis should be started as soon as possible, preferably within hours after exposure.
-The optimal duration of prophylaxis is unknown and may differ based on institution protocol.
-Current guidelines should be consulted for additional information.

Usual Pediatric Dose of Epzicom for HIV Infection:

At least 25 kg: 1 tablet orally once a day

Comments:
-Use of the individual components is recommended for patients less than 25 kg; the manufacturer product information for Epzicom should be consulted.
-Before prescribing this drug, the ability to swallow tablets should be assessed.

Use: In combination with other antiretroviral agents, for the treatment of HIV-1 infection

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Do not allow your medicine to run out completely before you get your prescription refilled. It is important that you not stop taking the medicine once you have started. If you miss several doses, you may have a dangerous or even fatal allergic reaction once you start taking this medication again.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Avoid drinking alcohol. It may increase your risk of liver damage or lactic acidosis.

Taking Epzicom will not prevent you from passing HIV to other people. Do not have unprotected sex or share razors or toothbrushes. Talk with your doctor about safe ways to prevent HIV transmission during sex. Sharing drug or medicine needles is never safe, even for a healthy person.

Stop using Epzicom and call your doctor at once if you have symptoms of an allergic reaction from two or more of these specific side effect groups:

• Group 1 - fever;

• Group 2 - rash;

• Group 3 - nausea, vomiting, diarrhea, stomach pain;

• Group 4 - general ill feeling, extreme tiredness, body aches;

• Group 5 - shortness of breath, cough, sore throat.

Once you have an allergic reaction to abacavir, you must never use it again. If you stop taking this medicine for any reason, talk to your doctor before you start taking it again.

Epzicom can also cause serious or fatal side effects on the liver. Call your doctor at once if you have:

• swelling around your midsection, upper stomach pain, unusual tiredness, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

Early symptoms of lactic acidosis may get worse over time and this condition can be fatal. Get emergency medical help if you have even mild symptoms: muscle pain or weakness, numb or cold feeling in your arms and legs, trouble breathing, stomach pain, nausea with vomiting, fast or uneven heart rate, dizziness, or feeling very weak or tired.

Epzicom may increase your risk of certain infections or autoimmune disorders by changing the way your immune system works. Symptoms may occur weeks or months after you start treatment with Epzicom. Tell your doctor if you have:

• signs of a new infection - fever, night sweats, swollen glands, mouth sores, diarrhea, stomach pain, weight loss;

• chest pain (especially when you breathe), dry cough, wheezing, feeling short of breath;

• cold sores, sores on your genital or anal area;

• rapid heart rate, feeling anxious or irritable, weakness or prickly feeling, problems with balance or eye movement;

• trouble speaking or swallowing, severe lower back pain, loss of bladder or bowel control; or

• swelling in your neck or throat (enlarged thyroid), menstrual changes, impotence, loss of interest in sex.

Common Epzicom side effects include:

• sleep problems (insomnia);

• headache, dizziness, tiredness, depression;

• nausea, diarrhea; or

• changes in the shape or location of body fat (especially in your arms, legs, face, neck, breasts, and trunk).

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Applies to abacavir / lamivudine: oral tablet

General

In 1 study, once- or twice-daily abacavir was used in combination with lamivudine and efavirenz. Patients receiving once-daily abacavir had a significantly higher incidence of severe drug hypersensitivity reactions and severe diarrhea than patients on the twice-daily regimen.

Many of the side effects listed occurred commonly in patients with abacavir hypersensitivity (e.g., nausea, vomiting, diarrhea, fever, lethargy, rash).[Ref]

Hypersensitivity

Serious and sometimes fatal hypersensitivity reactions have been reported with abacavir. Such reactions have included multi-organ failure and anaphylaxis and usually occurred within the first 6 weeks of abacavir therapy (median onset: 9 to 11 days); however, abacavir hypersensitivity reactions have occurred any time during therapy.

Patients with the human leukocyte antigen subtype B*5701 (HLA-B*5701) allele are at higher risk of abacavir hypersensitivity reactions; however, such reactions have occurred in patients without the HLA-B*5701 allele. Abacavir hypersensitivity was reported in about 8% of patients in 9 clinical trials with abacavir-containing products where patients were not screened for the HLA-B*5701 allele; incidence of suspected abacavir hypersensitivity reactions was 1% in clinical trials where HLA-B*5701 carriers were excluded.

Abacavir hypersensitivity reactions have been characterized by at least 2 of the following key signs/symptoms: (1) fever; (2) rash; (3) gastrointestinal symptoms (including nausea, vomiting, diarrhea, abdominal pain); (4) constitutional symptoms (including generalized malaise, fatigue, achiness); (5) respiratory symptoms (including dyspnea, cough, pharyngitis). Almost all reactions have included fever and/or rash (usually maculopapular or urticarial); however, reactions also reported without fever or rash. Signs/symptoms reported in at least 10% of patients with hypersensitivity reaction have included rash, nausea, vomiting, diarrhea, abdominal pain, dyspnea, cough, fever, fatigue/lethargy, malaise, headache, elevated liver function tests, and myalgia. Other signs/symptoms of hypersensitivity have included mouth ulceration, sore throat, adult respiratory distress syndrome, respiratory failure, edema, lymphadenopathy, hypotension, conjunctivitis, anaphylaxis, paresthesia, lymphopenia, hepatitis, liver failure, myolysis, arthralgia, elevated creatine phosphokinase, elevated creatinine, renal failure, abnormal chest x-ray findings (mainly infiltrates, which were localized), and death.

Symptoms of abacavir hypersensitivity reaction worsened with continued therapy and generally resolved when abacavir was discontinued. Restarting abacavir after a hypersensitivity reaction has resulted in more severe symptoms within hours and included life-threatening hypotension and death. Rarely, life-threatening reactions have occurred within hours after restarting abacavir in patients who stopped it for reasons other than symptoms of hypersensitivity (or who stopped it with only 1 key symptom of hypersensitivity).[Ref]

Abacavir and lamivudine:
-Common (1% to 10%): Drug hypersensitivity
-Postmarketing reports: Sensitization reactions (including anaphylaxis)

Abacavir:
-Common (1% to 10%): Hypersensitivity reactions (including fever, rash [maculopapular, urticarial], nausea, vomiting, diarrhea, abdominal pain, pharyngitis, malaise, fatigue, achiness, dyspnea, cough, lethargy, headache, myalgia, arthralgia, myolysis, edema, abnormal chest x-ray findings [mainly localized infiltrates], paresthesia, anaphylaxis, hepatitis, liver failure, renal failure, hypotension, sore throat, adult respiratory distress syndrome, respiratory failure, death, lymphadenopathy, mucous membrane lesions [conjunctivitis, mouth ulceration], erythema multiforme, elevated liver function tests, elevated creatine phosphokinase, elevated creatinine, lymphopenia)

Lamivudine:
-Frequency not reported: Anaphylactoid reactions[Ref]

Hepatic

Abacavir and lamivudine:
-Common (1% to 10%): Elevated ALT, elevated AST
-Uncommon (0.1% to 1%): Abnormal bilirubin
-Frequency not reported: Severe hepatomegaly with steatosis
-Postmarketing reports: Hepatic steatosis, posttreatment exacerbation of hepatitis B

Abacavir:
-Frequency not reported: Liver function test abnormalities, elevated GGT

Lamivudine:
-Uncommon (0.1% to 1%): Transient elevations in liver enzymes (AST, ALT)
-Rare (less than 0.1%): Hepatitis
-Frequency not reported: Elevated bilirubin, elevated hepatic enzymes, hepatic decompensation, severe acute exacerbations of hepatitis[Ref]

Lactic acidosis and severe hepatomegaly with steatosis (including fatal cases) have been reported with the use of nucleoside analogs.

Elevated GGT was observed in the expanded access program for abacavir.

Hepatic decompensation (some fatal) has been reported in patients coinfected with HIV-1 and hepatitis C virus receiving combination antiretroviral therapy for HIV-1 and interferon alfa with or without ribavirin.

Severe acute exacerbations of hepatitis have been reported in patients with hepatitis B after discontinuation of lamivudine.[Ref]

Gastrointestinal

Abacavir and lamivudine:
-Common (1% to 10%): Nausea, diarrhea, abdominal pain/gastritis, abnormal amylase
-Postmarketing reports: Stomatitis

Abacavir:
-Common (1% to 10%): Nausea, vomiting, diarrhea
-Postmarketing reports: Pancreatitis (rare)

Lamivudine:
-Common (1% to 10%): Nausea, vomiting, abdominal pain/cramps, diarrhea
-Frequency not reported: Elevated lipase
-Postmarketing reports: Elevated serum amylase (rare), pancreatitis (rare)[Ref]

Pancreatitis was observed in the expanded access program for abacavir.[Ref]

Dermatologic

Suspected Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported in patients using abacavir primarily in combination with agents known to be associated with SJS and TEN, respectively.

Cases of erythema multiforme, SJS, or TEN have been reported very rarely when abacavir hypersensitivity could not be ruled out.[Ref]

Abacavir and lamivudine:
-Common (1% to 10%): Rash
-Postmarketing reports: Alopecia, erythema multiforme, Stevens-Johnson syndrome, urticaria

Abacavir:
-Frequency not reported: Sweet's syndrome
-Postmarketing reports: Rash without systemic symptoms (common), erythema multiforme (very rare), Stevens-Johnson syndrome (very rare), toxic epidermal necrolysis (very rare)

Lamivudine:
-Common (1% to 10%): Rash
-Rare (less than 0.1%): Angioedema
-Frequency not reported: Pruritus, urticaria
-Postmarketing reports: Alopecia (common)[Ref]

Hematologic

Abacavir and lamivudine:
-Common (1% to 10%): Abnormal absolute neutrophils
-Uncommon (0.1% to 1%): Abnormal hemoglobin, abnormal platelets, abnormal WBC
-Postmarketing reports: Aplastic anemia, anemia (including pure red cell aplasia and severe anemias progressing on therapy), lymphadenopathy, splenomegaly

Abacavir:
-Frequency not reported: Anemia, neutropenia, agranulocytosis

Lamivudine:
-Uncommon (0.1% to 1%): Thrombocytopenia, neutropenia, anemia
-Postmarketing reports: Pure red cell aplasia (very rare)[Ref]

Agranulocytosis has been reported after the addition of abacavir to a multi-drug regimen.

Occasionally, neutropenia and anemia reported with lamivudine were severe.[Ref]

Nervous system

Abacavir and lamivudine:
-Common (1% to 10%): Headache/migraine, dizziness/vertigo
-Postmarketing reports: Peripheral neuropathy, paresthesia, seizures

Abacavir:
-Common (1% to 10%): Headache

Lamivudine:
-Common (1% to 10%): Headache
-Postmarketing reports: Paresthesia (very rare), peripheral neuropathy (very rare)[Ref]

Other

The emergence of lamivudine-resistant HBV has been reported in HIV-1/HBV-coinfected patients using lamivudine-containing antiretroviral regimens.[Ref]

Abacavir and lamivudine:
-Common (1% to 10%): Fatigue/malaise, pyrexia
-Postmarketing reports: Weakness

Abacavir:
-Common (1% to 10%): Fever, lethargy, fatigue

Lamivudine:
-Common (1% to 10%): Fatigue, malaise, fever
-Frequency not reported: Drug-resistant hepatitis B virus (HBV)[Ref]

Psychiatric

Abacavir and lamivudine:
-Common (1% to 10%): Insomnia, depression/depressed mood, abnormal dreams, anxiety

Lamivudine:
-Common (1% to 10%): Insomnia[Ref]

Metabolic

Lactic acidosis and severe hepatomegaly with steatosis (including fatal cases) have been reported with the use of nucleoside analogs.

Redistribution/accumulation of body fat has been reported with antiretroviral therapy; causality has not been established.[Ref]

Abacavir and lamivudine:
-Common (1% to 10%): Abnormal triglycerides
-Uncommon (0.1% to 1%): Abnormal alkaline phosphatase, abnormal glucose, abnormal sodium
-Frequency not reported: Lactic acidosis
-Postmarketing reports: Hyperglycemia, redistribution/accumulation of body fat

Abacavir:
-Common (1% to 10%): Anorexia
-Frequency not reported: Elevated blood glucose, elevated triglycerides
-Postmarketing reports: Hyperlactatemia (common), lactic acidosis (rare)

Lamivudine:
-Postmarketing reports: Hyperlactatemia (common), lactic acidosis (rare)

Combination antiretroviral therapy:
-Frequency not reported: Redistribution/accumulation of body fat (including central obesity, dorsocervical fat enlargement, peripheral wasting, facial wasting, breast enlargement, "cushingoid appearance"), metabolic abnormalities (e.g., hypertriglyceridemia, hypercholesterolemia, insulin resistance, hyperglycemia, hyperlactatemia)[Ref]

Musculoskeletal

Abacavir and lamivudine:
-Uncommon (0.1% to 1%): Abnormal creatine phosphokinase (CPK)
-Postmarketing reports: Muscle weakness, CPK elevation, rhabdomyolysis

Abacavir:
-Frequency not reported: Elevated CPK

Lamivudine:
-Postmarketing reports: Arthralgia (common), muscle disorders (common), rhabdomyolysis (rare)

Combination antiretroviral therapy:
-Frequency not reported: Osteonecrosis[Ref]

Cardiovascular

Abacavir:
-Postmarketing reports: Myocardial infarction (MI)

An observational study investigating the rate of MI in patients on combination antiretroviral therapy showed an increased risk of MI with the use of abacavir within the previous 6 months. A sponsor-conducted pooled analysis of clinical trials showed no excess risk of MI in abacavir-treated patients as compared with control subjects. Overall, available data from the observational cohort and from clinical trials were inconclusive.

Immunologic

Frequency not reported: Immune reconstitution/reactivation syndrome, autoimmune disorders in the setting of immune reconstitution (e.g., Graves' disease, polymyositis, Guillain-Barre syndrome)

Renal

Abacavir and lamivudine:
-Uncommon (0.1% to 1%): Abnormal creatinine[Ref]

Respiratory

Abacavir and lamivudine:
-Postmarketing reports: Abnormal breath sounds/wheezing

Lamivudine:
-Common (1% to 10%): Cough, nasal symptoms[Ref]

Some side effects of Epzicom may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.